Ethionamide (ETH) is part of the drug arsenal available to treat multi-drug resistant tuberculosis. The current paradigm of this pro-drug activation involves the mycobacterial enzyme EthA and the transcriptional repressor, EthR. However, several lines of evidence suggest the involvement of additional players. The ethA/R locus was deleted in Mycobacterium bovis BCG and three Mycobacterium tuberc...

AIMS The aim of this animal study is to assess fasting-induced changes in myocardial substrate metabolism and energy status as a consequence of mitochondrial long-chain fatty acid β-oxidation deficiency, using magnetic resonance spectroscopy (MRS). METHODS AND RESULTS Carbon-13 ((13)C) MRS of hyperpolarized [1-(13)C]pyruvate was used to assess in vivo pyruvate dehydrogenase (PDH) activity in ...

Melanocortin-3 and 4 receptors (MC3R and MC4R) can regulate energy homeostasis, but their respective roles especially the functions of MC3R need more exploration. Here Mc3r and Mc4r single and double knockout (DKO) rats were generated using CRISPR-Cas9 system. Metabolic phenotypes were examined and data were compared systematically. Mc3r KO rats displayed hypophagia and decreased body weight, w...

Renalase is a kidney-secreted catecholamines-degrading enzyme whose expression and activity are downregulated by increased dietary phosphate. A renalase knockout (KO) mouse model was used to explore the mechanisms mediating renalase's effect on phosphate excretion. Compared with wild-type (WT) mice maintained on a regular diet, KO mice show decreased serum PO4(-) (KO = 5.3 ± 0.2 vs. WT = 6.0 ± ...

Nitric oxide (NO) modulates renal blood flow (RBF) and kidney function and is involved in blood pressure (BP) regulation predominantly via stimulation of the NO-sensitive guanylyl cyclase (NO-GC), existing in two isoforms, NO-GC1 and NO-GC2. Here, we used isoform-specific knockout (KO) mice and investigated their contribution to renal hemodynamics under normotensive and angiotensin II-induced h...

Inherited defects in purine nucleoside phosphorylase (PNP) cause severe T cell immunodeficiency and progressive neurological dysfunction, yet little is known about the effects of PNP deficiency on the brain. PNP-KO mice display metabolic and immune anomalies similar to those observed in patients. Our objectives were to characterize brain abnormalities in PNP-KO mice and determine whether restor...

The specific roles of nitric oxide (NO) synthases (NOSs) in bladder smooth muscle remain to be elucidated. We examined the roles of NOSs in β-adrenoceptor (AR)-mediated bladder relaxation. Male mice (C57BL6) deficient of neuronal NOS [nNOS-knockout (KO)], endothelial NOS (eNOS-KO), neuronal/endothelial NOS (n/eNOS-KO), neuronal/endothelial/inducible NOS (n/e/iNOS-KO), and their controls [wild-t...

Ecker, Phillip M., Chu-Chuan Lin, Jennifer Powers, Brian K. Kobilka, Anne M. Dubin, and Daniel Bernstein. Effect of targeted deletions of !1and !2-adrenergic-receptor subtypes on heart rate variability. Am J Physiol Heart Circ Physiol 290: H192–H199, 2006. First published August 19, 2005; doi:10.1152/ajpheart.00032.2005.— !-Adrenergic receptors (!-ARs) play a major role in regulating heart rate...

Gastrin, a potent stimulator of gastric acid secretion, primarily targets the acid-secreting parietal cells and histamine-secreting enterochromaffin-like (ECL) cells in the stomach. Accordingly, gastrin-deficient (GAS-KO) mice have a severe impairment in acid secretion. The aim of this study was to characterize changes in gene expression in GAS-KO mice to identify gastrin-regulated genes and to...